In 1981, cancer has become the leading cause of death in Japan, and has remained the leading cause of death since then. Thus, there is continuous demand for novel cancer therapy. Currently employed cancer therapies include surgical therapy, radiotherapy, and chemotherapy (by means of anti-cancer agents). Even after surgical operation, a cancer therapy by an anti-cancer agent is also employed.
Examples of anti-cancer agents currently employed include an alkylating agent, a metabolic antagonist, an alkaloid anti-cancer agent, an antibiotic anti-cancer agent, and a platinum drug. However, the therapeutic effects of the anti-cancer agents are not sufficient at present, and adverse side effects often arise, which are problematic. From this viewpoint, development of a more improved anti-cancer agent is envisaged.
Meanwhile, MFG-E8 (a milk fat globule membrane glycoprotein: milk fat globule-EGF factor 8) was previously identified as a factor which is secreted through the mammary gland and which promotes differentiation of the mammary gland and suckling stimulation (Non-Patent Document 1). In recent years, in addition to the above actions, MFG-E8 has been found to have a variety of functions. Among them, one important function thereof is that MFG-E8 serves as an opsonin which recognizes phosphatidylserine present on the surfaces of apoptotic cells, to thereby promote the phagocytic activity of macrophages and dendritic cells, whereby immune tolerance is maintained (Non-Patent Documents 2, 3). Furthermore, MFG-E8 is known to promote growth of Foxp 3-positive-regulatory T cells, to thereby induce tolerance, whereby the antitumor immunity of an anti-tumor vaccine is negatively controlled (Non-Patent Document 4). On the basis of these findings, a therapeutic method employing a decoy gene of MFG-E8 and an anti-MFG-E8 antibody were previously developed with the aim of combined use with a tumor antigen such as a cancer vaccine, and a patent application was filed (Patent Document 1). Also, studies revealed that MFG-E8 is widely expressed not only in antigen-presenting cells such as dendritic cells but also in cells of a tumor (e.g., breast cancer, colon carcinoma, or melanoma) (Non-Patent Document 5), and that MFG-E8 has a tumor-activating action through promoting angiogenesis and tumor metastasis and positively correlates with the clinical progress of melanoma (Non-Patent Document 6).